Notochordal remnants in human iniencephaly suggest disturbed dorsoventral axis signaling

Iniencephaly is a central nervous system malformation in which brain and sp inal cord are not normally separated at the level of the foramen magnum. Th e occipital region is fastened to the back of the body at different levels. The purpose of this study of a le-week. human fetus with iniencephaly and holoprosencephaly was to examine the body axis for notochordal remnants in order to determine if an abnormality of dorsoventral axis signaling may be responsible for the development of the iniencephaly abnormality. This aspec t of iniencephaly has not been described previously. Radiographic and histo chemical investigations were performed, The fetus described here appeared t o exhibit an abnormal notochordal course in the upper lumbar, thoracic, and cervical regions. This finding leads us to the hypothesis that iniencephal y might arise because of deviant gene expression in the embryonic period af fecting the dorsoventral orientation of the body axis, anatomically indicat ed by the notochordal malpositions. Am. J. Med, Genet. 84:425-432, 1999. (C ) 1999 Wiley-Liss, Inc.